CAJ | 학술논문

背景:许多研究表明淀粉样β蛋白在阿尔茨海默病的发病中起着主要的作用,淀粉样β蛋白的减少将延缓阿尔茨海默病的发展,因此减少淀粉样β蛋白的产生成为干预阿尔茨海默病的一项重要策略.许多阿尔茨海默病患者因精神行为异常而接受抗精神病药物治疗,非典型抗精神病药物奥氮平与喹硫平能够明显地改善阿尔茨海默病患者临床整体印象评分,早期开始的长期干预能够改善患者预后.目的:观察奥氮平与喹硫平对双转染(瑞典淀粉样β蛋白前体蛋白基因和早老素1基因)鼠成神经瘤细胞分泌淀粉样β蛋白42的作用.设计:以细胞为研究对象,完全随机分组设计,对照实验研究.材料:所有研究工作均在加拿大萨斯卡彻温大学医学院神经精神研究所进行.鼠N2a成神经瘤细胞与双转染N2a细胞由康奈尔大学医学院神经病学及神经科学系提供.干预:双转染N2a细胞分别予200 μmol/L奥氮平及50μmol/L喹硫平处理24 h后,应用酶联免疫吸附反应法测定细胞内外淀粉样β蛋白的水平.应用四甲基偶氮唑盐方法检测细胞活性、BCA法测定细胞的蛋白质含量、免疫印迹检测N2a与双转染N2a细胞淀粉样β蛋白前体蛋白的表达、酶联免疫吸附法测定双转染N2a细胞分泌到培养液及细胞内的淀粉样β蛋白42水平.主要观察指标:测定双转染N2a细胞分泌到培养液及细胞内的淀粉样β蛋白42水平.结果:双转染N2a细胞淀粉样β蛋白前体蛋白的表达明显高于N2a细胞.奥氮平处理组细胞外淀粉样β蛋白浓度[(4.78±0.54)nmol/L]明显低于对照组[(7.69±0.62)nmol/L](t=3.52,P＜0.05);喹硫平处理组细胞外淀粉样β蛋白浓度[(4.09±0.18)nmol/L]明显低于对照组[(7.50±0.50)nmol/L](t=5.61,P＜0.05).奥氮平处理组细胞内淀粉样β蛋白浓度与对照组比较,差异无显著性意义(P＞0.05);喹硫平处理组细胞内淀粉样β蛋白浓度与对照组比较,差异无显著性意义(P＞0 05).结论:奥氮平与喹硫平能够减少双转染鼠N2a细胞外淀粉样β蛋白42的分泌,奥氮平与喹硫平的应用有可能通过减少神经细胞淀粉样β蛋白42的分泌延缓阿尔茨海默病的发展. 揹景:許多研究錶明澱粉樣β蛋白在阿爾茨海默病的髮病中起著主要的作用,澱粉樣β蛋白的減少將延緩阿爾茨海默病的髮展,因此減少澱粉樣β蛋白的產生成為榦預阿爾茨海默病的一項重要策略.許多阿爾茨海默病患者因精神行為異常而接受抗精神病藥物治療,非典型抗精神病藥物奧氮平與喹硫平能夠明顯地改善阿爾茨海默病患者臨床整體印象評分,早期開始的長期榦預能夠改善患者預後.目的:觀察奧氮平與喹硫平對雙轉染(瑞典澱粉樣β蛋白前體蛋白基因和早老素1基因)鼠成神經瘤細胞分泌澱粉樣β蛋白42的作用.設計:以細胞為研究對象,完全隨機分組設計,對照實驗研究.材料:所有研究工作均在加拿大薩斯卡徹溫大學醫學院神經精神研究所進行.鼠N2a成神經瘤細胞與雙轉染N2a細胞由康奈爾大學醫學院神經病學及神經科學繫提供.榦預:雙轉染N2a細胞分彆予200 μmol/L奧氮平及50μmol/L喹硫平處理24 h後,應用酶聯免疫吸附反應法測定細胞內外澱粉樣β蛋白的水平.應用四甲基偶氮唑鹽方法檢測細胞活性、BCA法測定細胞的蛋白質含量、免疫印跡檢測N2a與雙轉染N2a細胞澱粉樣β蛋白前體蛋白的錶達、酶聯免疫吸附法測定雙轉染N2a細胞分泌到培養液及細胞內的澱粉樣β蛋白42水平.主要觀察指標:測定雙轉染N2a細胞分泌到培養液及細胞內的澱粉樣β蛋白42水平.結果:雙轉染N2a細胞澱粉樣β蛋白前體蛋白的錶達明顯高于N2a細胞.奧氮平處理組細胞外澱粉樣β蛋白濃度[(4.78±0.54)nmol/L]明顯低于對照組[(7.69±0.62)nmol/L](t=3.52,P＜0.05);喹硫平處理組細胞外澱粉樣β蛋白濃度[(4.09±0.18)nmol/L]明顯低于對照組[(7.50±0.50)nmol/L](t=5.61,P＜0.05).奧氮平處理組細胞內澱粉樣β蛋白濃度與對照組比較,差異無顯著性意義(P＞0.05);喹硫平處理組細胞內澱粉樣β蛋白濃度與對照組比較,差異無顯著性意義(P＞0 05).結論:奧氮平與喹硫平能夠減少雙轉染鼠N2a細胞外澱粉樣β蛋白42的分泌,奧氮平與喹硫平的應用有可能通過減少神經細胞澱粉樣β蛋白42的分泌延緩阿爾茨海默病的髮展.
배경:허다연구표명정분양β단백재아이자해묵병적발병중기착주요적작용,정분양β단백적감소장연완아이자해묵병적발전,인차감소정분양β단백적산생성위간예아이자해묵병적일항중요책략.허다아이자해묵병환자인정신행위이상이접수항정신병약물치료,비전형항정신병약물오담평여규류평능구명현지개선아이자해묵병환자림상정체인상평분,조기개시적장기간예능구개선환자예후.목적:관찰오담평여규류평대쌍전염(서전정분양β단백전체단백기인화조로소1기인)서성신경류세포분비정분양β단백42적작용.설계:이세포위연구대상,완전수궤분조설계,대조실험연구.재료:소유연구공작균재가나대살사잡철온대학의학원신경정신연구소진행.서N2a성신경류세포여쌍전염N2a세포유강내이대학의학원신경병학급신경과학계제공.간예:쌍전염N2a세포분별여200 μmol/L오담평급50μmol/L규류평처리24 h후,응용매련면역흡부반응법측정세포내외정분양β단백적수평.응용사갑기우담서염방법검측세포활성、BCA법측정세포적단백질함량、면역인적검측N2a여쌍전염N2a세포정분양β단백전체단백적표체、매련면역흡부법측정쌍전염N2a세포분비도배양액급세포내적정분양β단백42수평.주요관찰지표:측정쌍전염N2a세포분비도배양액급세포내적정분양β단백42수평.결과:쌍전염N2a세포정분양β단백전체단백적표체명현고우N2a세포.오담평처리조세포외정분양β단백농도[(4.78±0.54)nmol/L]명현저우대조조[(7.69±0.62)nmol/L](t=3.52,P＜0.05);규류평처리조세포외정분양β단백농도[(4.09±0.18)nmol/L]명현저우대조조[(7.50±0.50)nmol/L](t=5.61,P＜0.05).오담평처리조세포내정분양β단백농도여대조조비교,차이무현저성의의(P＞0.05);규류평처리조세포내정분양β단백농도여대조조비교,차이무현저성의의(P＞0 05).결론:오담평여규류평능구감소쌍전염서N2a세포외정분양β단백42적분비,오담평여규류평적응용유가능통과감소신경세포정분양β단백42적분비연완아이자해묵병적발전.
BACKGROUND: Many studies have indicated that amyloid beta-protein (Aβ) plays an important role in the pathophysiology of Alzheimer disease (AD), the reduction of production of Aβ can slow down the deterioration of AD, so to reduce Aβ production could become an important therapeutic target in AD. Many AD patients present behavioral disturbance and psychotic symptoms, and are treated with antipsychotics. Olanzapine and quetiapine can significantly improve the clinical global impressions(CGI) severity-of-Alzheimer scores, clinical studies suggest that early and prolonged intervention can improve long-term outcome.OBJECTIVE: To investigate the effect of olanzapine and quetiapine on the secretion of Aβ42 in Swedish amyloid precursor protein(APP) gene and presenilin 1 gene transfected murine N2a neuroblastoma cells.DESIGN: A completely randomized controlled trial based on N2a cells.MATERIALS: Setting was at Neuropsychiatry Research Institute of Medical College, University of Saskatchewan. The murine N2a and double transfected N2a cell was provided by department of neurology and neuroscience, Cornell university medical college.INTERVENTIONS: The double transfected murine N2a neuroblastoma cells were treated for 24 hours with 200 μmol/L olanzapine and 50 μ mol/L quetiapine respectively, then intracellular and extrocellular levels of Aβ were determined. The MTT assay was used to determine cell viability; the BCA assay was used to determine the protein content of cells; the western blot analysis was used to determine the APP expression; and the Enzyme-Linked-Immuno-Sorbent Assay(ELISA) was used to determine the Aβ produced by double transfected murine N2a neuroblastoma cells.MAIN OUTCOME MEASURES: The levels of intracellular and extracellullar Aβ 42 secreted by double transfected murine N2a neuroblastoma cells were detected using ELISA.RESULTS: The double transfected N2a cells produced more APPs than the naive N2a cells. The extracellular Aβ[ (4.78 ± 0.54) nmol/L] of cells treated with olanzapine decreased significantly comparing to the vehicle [(7.69±0.62) nmol/L] (t=3.52, P ＜0.05); and theextracellular Aβ[ (4. 09 ±0. 18) nmol/L] of cells treated with quetiapine decreased significantly comparing to the vehicle[ (7.50 ±0.50) nmol/L] ( t =5.61,P ＜ 0.05) . The intracellular Aβ of cells treated with olanzapine did not change significantly conpared with the vehicle ( P ＞ 0.05 ); the intracellular Aβ of cells treated with quetiapine did not change significantly compared with the vehicle ( P ＞ 0.05 ).CONCLUSION: The result suggests that olanzapine and quetiapine can decrease the production of Aβ42 in double transfected murine N2a neuroblastoma cells and clinically may be helpful in slowing down the progression of AD by decreasing the extrocellular secretion of Aβ42.